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Rimonabant Studied for Heart Disease & Alcohol Consumption Blocking
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Researchers Study Multi-purpose Drug for Benefits to Heart Disease
2/1/06
Researchers at the University of Rochester Medical Center today announced that they have launched a study to determine whether an experimental drug, rimonabant, can slow atherosclerosis, the fatty build-up in arteries that creates heart attack risk. In recent studies, rimonabant has been shown to decrease body weight, improve abnormal levels of blood sugars and fats (cholesterol) and to help willing patients quit smoking. Now researchers hope to add coronary artery disease (CAD), atherosclerosis within the arteries of the heart, to the list of maladies addressed. A decision on whether rimonabant is safe and effective and if so, for which uses, is expected from the U.S. Food and Drug Administration in 2006.
Unlike previous cholesterol drugs that treat some aspect of blood or blood vessel walls, rimonabant is a cannabinoid receptor antagonist, which exerts its effect in parts of the brain that control appetite and addictive behaviors. Results of previous studies show that rimonabant reduces triglycerides and increases HDL-C, or "good" cholesterol, independent of weight loss. The new study, titled STADIVARIUS (Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant- The Intravascular Ultrasound Study), will explore whether these effects will impact the progression of atherosclerosis.
"Obesity, diabetes, high cholesterol and coronary artery disease have all reached epidemic proportions to become leading causes of death despite being largely preventable," said Frederick S. Ling, M.D., director of the Cardiac Catheterization Laboratory, associate professor of Medicine at the medical center and principal investigator for STRADIVARIUS. "These risk factors, called metabolic syndrome when combined in one person, feed off each other and are made much worse by smoking. New approaches are urgently needed, and our lab has the tools to measure accurately whether new treatments actually slow the progression of coronary artery disease."
Specifically, people with metabolic syndrome have at least three of the following risk factors: abdominal obesity, high blood pressure, insulin resistance/high blood sugar (precursor to diabetes), and blood lipid disorders (high triglycerides or low good cholesterol (HDL-C)). The 50 million Americans with the syndrome are at increased risk for CAD, which takes 500,000 lives per year, according to the American Heart Association. By further worsening disease in coronary arteries, smoking puts 47 million Americans at even greater risk.
Study Details
STRADIVARIUS is a randomized, placebo-controlled, phase III research study that has almost completed enrollment. The study goal is to enroll 800 patients worldwide, including 500 from the United States and 10 in Rochester. Patients are randomized to receive either placebo or a 20 mg tablet of rimonabant (proposed trade name: Acomplia) daily for an 18-month period.
The progress of coronary artery disease will be measured by using intravascular ultrasound (IVUS) when patients are referred initially for a coronary angiogram. At their 18-month visit, a repeat IVUS will be performed. IVUS is a newer imaging technique that uses computer analysis of ultrasound energy to capture images of the insides of blood vessels. Researchers believe it has the potential to more accurately measure the degree of narrowing (stenosis) and plaque build-up (fatty deposits) within an artery than x-ray-based techniques.
To qualify for the study, patients must be referred by their physicians to undergo a coronary angiogram. Patients qualify if there is a 20 percent, but less than 50 percent, stenosis in one of their coronary arteries (mild CAD). Stenosis is an abnormal narrowing in a blood vessel, an effect of damaging deposits (cholesterol, calcium) within arterial walls.
If the narrowing leads to blockage by a blood clot of a coronary artery, heart attack occurs. Only patients with mild CAD will be included in STRADIVARIUS because those with an artery more than 50 percent closed may need treatment for the blockage, such as angioplasty (balloon or stent) or heart bypass surgery.
While enrollment in the study is closed locally, those interested can find more information about STADIVARIUS and the catheterization lab by visiting their website below.
1.Recruiting Rimonabant to Reduce Alcohol Consumption
Conditions: Healthy; Alcohol Drinking
2.Recruiting Atherosclerosis Underlying Development Assessed By Intima-Media Thickness In Patients On Rimonabant (Auditor)
Conditions: Carotid Artery Plaque; Arteriosclerosis; Obesity; Metabolic Syndrome
3.Recruiting CRESCENDO Comprehensive Rimonabant Evaluation Study of Cardiovascular ENDpoints and Outcomes
Condition: Cardiovascular Disease
Rimonabant to Reduce Alcohol Consumption
This study is currently recruiting patients.
Verified by National Institutes of Health Clinical Center (CC) March 14, 2005 Sponsored by: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00075205
phase II Study of Rimonabant for patients who are healthy but who drink alcohol
Purpose This study will examine whether Rimonabant, a drug that blocks cannabinoid-1 (CB1) receptors in the brain, affects alcohol consumption. Substances called endocannabinoids, which have many of the same effects of marijuana, bind to CB1 receptors. Animal studies show that when CB1 receptors are blocked, the animals consume less alcohol.
Healthy normal volunteers between 21 and 40 years of age who consume between 20 and 40 alcoholic drinks per week, drink at least 4 days a week, and are not seeking treatment for alcoholism may be eligible for this study. Candidates are screened with a medical history, including questions about alcohol and drug use, physical examination, blood and urine tests, breath alcohol test, and electrocardiogram.
Participants are asked about their mental health history and use of alcohol, cigarettes and illicit drugs, and fill out questionnaires evaluating their emotional state and personality. Then, they begin a baseline evaluation in which they call a number at the NIH Clinical Center for 21 days to report how much alcohol they drank that day. One week after starting the baseline evaluation, they are randomly assigned to take either Rimonabant or placebo (a pill with no active ingredient) for 2 weeks. Before starting the drug, they have a urine drug screen and measurement of blood alcohol level. After 1 week on the test medication, they return to the Clinical Center to monitor drug or placebo side effects, if any, and to have a blood alcohol level test, urine drug screen, and blood tests for routine blood chemistries. After 2 weeks on the test medication, they come to the Clinical Center at noon for an alcohol self-administration test. Before the test, they are given a breath alcohol test and a urine drug test. The results of both tests must be negative to continue in the study.
The alcohol self-administration test is videotaped. A heparin lock is placed in a vein in the participant's arm. This small needle remains in the arm for the duration of the study to avoid multiple needle sticks for blood draws. Blood is drawn periodically during the test to determine routine laboratory values, cotinine level (assessment of smoking status), the amount of Rimonabant or placebo in the body, and levels of various hormones. Thirty minutes before the test begins and every 30 minutes during the test, participants complete questionnaires and rating scales regarding their mood and desire to drink. Five minutes before the test begins, a blood sample is drawn as a baseline measure to determine the amount of alcohol in the body before beginning the test and to examine the effects of the drug and the alcohol on various hormone levels. At 4 p.m., participants are given an alcoholic drink that they must drink within 5 minutes. They are monitored for the next 50 minutes, during which time they fill out rating scales. At 4:50 p.m., they are presented with four drinks and are given the option to drink as many of the drinks as they like or to receive $3.00 for each drink they do not consume. At 5:50 p.m., the drinks are removed, and at 6:00 p.m. four fresh, new drinks are presented with the same condition - to drink them or receive money for them. The study ends at 7 p.m. Participants are required to stay overnight in the hospital. The next morning, they are given breakfast, their vital signs are checked, they meet with staff to discuss risks associated with heavy alcohol use and are encouraged to participate in an alcohol treatment program. They are given a list of treatment programs and are offered assistance in making arrangements for treatment, if desired. They are then discharged from the hospital at about 9:00 a.m.
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